ABSTRACT Patients undergoing epilepsy surgery without evidence of a lesion on MR imaging and without a temporal source for seizure onset generally have less favorable outcomes than patients with structural lesions or temporal onset. However, many of these patients are viable candidates for invasive monitoring and subsequent resection or multiple subpial transections (MSTs). The purpose of this study was to evaluate the surgical treatment of pediatric patients with extratemporal, nonlesional epilepsy in order to better understand the clinical and neuropsychological outcomes expected in this patient group.
Forty-three pediatric patients with negative results on MR imaging and lateralized, extratemporal findings on electroencephalography underwent invasive monitoring with grid and/or strip electrodes. Thirty-three subsequently had resection of an epileptogenic focus and/or MSTs.
Outcome was classified as Engel class I or II in 54.5% of the patients who underwent resection/MSTs and Engel class III or IV in 45.5%. Use of MSTs was associated with poor outcome. Neuropsychological evaluation showed significant improvement in immediate auditory attention following surgery and revealed several significant results on subgroup analysis. Complications occurred in 14% of patients (a 7% rate per procedure). Ten patients (23%) underwent invasive monitoring without proceeding to therapeutic surgery because no epileptogenic region was amenable to resection. Neuropsychological outcomes were generally stable.
Patients with extratemporal, nonlesional seizures are viable candidates for invasive monitoring with grid/strip electrodes, and good outcomes can be obtained with resective surgery. The use of MSTs may correlate with worse outcome. This study also provides additional data to assist in counseling patients on the risks of negative invasive monitoring, deficits resulting from resection/MSTs, and possible operative complications.

[Show abstract][Hide abstract]ABSTRACT:
The aim of this article was to review and evaluate the published literature related to the outcome of epilepsy surgery, while placing it in an historical perspective, and to describe the future prospects in this field.

[Show abstract][Hide abstract]ABSTRACT:
Objective
In recent decades intracranial EEG (iEEG) recordings using increasing numbers of electrodes, higher sampling rates, and a variety of visual and quantitative analyses have indicated the presence of widespread, high frequency ictal and preictal oscillations (HFOs) associated with regions of seizure onset. Seizure freedom has been correlated with removal of brain regions generating pathologic HFOs. However, quantitative analysis of preictal HFOs has seldom been applied to the clinical problem of planning the surgical resection. We performed Granger causality (GC) analysis of iEEG recordings to analyze features of preictal seizure networks and to aid in surgical decision making.Methods
Ten retrospective and two prospective patients were chosen on the basis of individually stereotyped seizure patterns by visual criteria. Prospective patients were selected, additionally, for failure of those criteria to resolve apparent multilobar ictal onsets. iEEG was recorded at 500 or 1,000 Hz, using up to 128 surface and depth electrodes. Preictal and early ictal GC from individual electrodes was characterized by the strength of causal outflow, spatial distribution, and hierarchical causal relationships.ResultsIn all patients we found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning 2–42 s before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources, and contributed to planning of more limited surgical resections. Both patients have a class 1 outcome at 1 year.SignificanceGC analysis of iEEG has the potential to increase understanding of preictal network activity, and to help improve surgical outcomes in cases of otherwise ambiguous iEEG onset.

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J Neurosurg: Pediatrics / Volume 7 / February 2011 J Neurosurg Pediatrics 7:000–000, 2011J Neurosurg Pediatrics 7:179–188, 2011179179Tepilepsy patients, in particular, fare better with surgery, achieving 58% seizure freedom in the first year as com-pared with 8% in the medically treated group.30 Further, patients with demonstrable lesions on preoperative MR imaging also showed favorable outcomes with surgery. Several studies have demonstrated significantly higher rates of postoperative seizure freedom with “lesional” he efficacy of surgical therapy in certain types of epilepsy has been well established. A randomized controlled trial has demonstrated that temporal epilepsy as opposed to “nonlesional” cases in tempo-ral,5,12,14 extratemporal,33 and combined23 series. However, the prognosis for seizure amelioration in patients without temporal epileptogenesis or recognizable radiographic lesions seems less certain. Two recent studies highlighted the difficulty in surgically treating extratemporal, nonle-sional epilepsy. In one study7 involving 70 patients with nonlesional epilepsy based on both MR imaging and histopathology, the authors reported that Engel Class I or II outcomes were achieved in only 33% of the extra-temporal or temporal neocortical resection group com-pared with 70% of the patients who underwent standard temporal lobectomy. Similarly, in a study of 399 patients undergoing epilepsy surgery,9 significantly worse long-Extratemporal, nonlesional epilepsy in children: postsurgical clinical and neurocognitive outcomesClinical articleIan G. DorwarD, M.D.,1,2 Jeffrey B. TITus, Ph.D.,1,3,4 DavID D. LIMBrIck, M.D., Ph.D.,1,2 JaMes M. JohnsTon, M.D.,1,2 Mary e. BerTranD, M.D.,1,4 anD MaTThew D. sMyTh, M.D.,1,21Pediatric Epilepsy Center and 3Department of Psychology, St. Louis Children’s Hospital; Departments of 2Neurosurgery and 4Neurology, Washington University School of Medicine, St. Louis, MissouriObject. Patients undergoing epilepsy surgery without evidence of a lesion on MR imaging and without a tempo-ral source for seizure onset generally have less favorable outcomes than patients with structural lesions or temporal onset. However, many of these patients are viable candidates for invasive monitoring and subsequent resection or multiple subpial transections (MSTs). The purpose of this study was to evaluate the surgical treatment of pediatric patients with extratemporal, nonlesional epilepsy in order to better understand the clinical and neuropsychological outcomes expected in this patient group.Methods. Forty-three pediatric patients with negative results on MR imaging and lateralized, extratemporal findings on electroencephalography underwent invasive monitoring with grid and/or strip electrodes. Thirty-three subsequently had resection of an epileptogenic focus and/or MSTs.Results. Outcome was classified as Engel class I or II in 54.5% of the patients who underwent resection/MSTs and Engel class III or IV in 45.5%. Use of MSTs was associated with poor outcome. Neuropsychological evaluation showed significant improvement in immediate auditory attention following surgery and revealed several significant results on subgroup analysis. Complications occurred in 14% of patients (a 7% rate per procedure). Ten patients (23%) underwent invasive monitoring without proceeding to therapeutic surgery because no epileptogenic region was amenable to resection. Neuropsychological outcomes were generally stable.Conclusions. Patients with extratemporal, nonlesional seizures are viable candidates for invasive monitoring with grid/strip electrodes, and good outcomes can be obtained with resective surgery. The use of MSTs may correlate with worse outcome. This study also provides additional data to assist in counseling patients on the risks of negative invasive monitoring, deficits resulting from resection/MSTs, and possible operative complications. (DOI: 10.3171/2010.11.PEDS10265)key worDs • epilepsy surgery • invasive subdural electrode monitoring • Engel class outcome • electrocorticographyAbbreviations used in this paper: AED = antiepileptic drug; ECoG = electrocorticography; EEG = electroencephalogram; MST = multiple subpial transection.

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I. G. Dorward et al.180 J Neurosurg: Pediatrics / Volume 7 / February 2011term outcomes were noted in patients with extratemporal (42% vs 74% Class I) or pathologically normal (62% vs 79% Class I) resections. Another study17 of pediatric pa-tients showed 85% Engel Class I outcomes for temporal versus 60% for extratemporal resections, though all cases involved a pathological lesion.We sought to evaluate outcomes of pediatric epilepsy surgery in patients whose EEGs showed lateralizing find-ings but no temporal source, and whose MR images dem-onstrated no potentially epileptogenic lesions. Though studies have suggested that resective surgery for patients with normal MR imaging studies,15 even when the source is extratemporal,10,29 can yield satisfactory results, these patients continue to pose a significant challenge to the epilepsy surgery team. We hypothesize that pediatric pa-tients with extratemporal, nonlesional epilepsy will ben-efit from resective surgery in appropriate cases.MethodsFollowing institutional review board approval, we retrospectively reviewed the records of 141 consecutive patients who presented to St. Louis Children’s Hospital for invasive monitoring with subdural grid/strip electrode placement between October 1994 and September 2007. Of these, we identified 43 patients who did not undergo temporal surgery (whether resection or MST), and whose MR imaging scans demonstrated no abnormality that corresponded with a likely seizure focus. All patients were monitored with invasive video ECoG for a period of 3–21 days. Of these initial 43 patients in our study group, 33 underwent resection of an epileptogenic focus or, if the area in question involved eloquent cortex, multiple sub-pial transections (MSTs). One of these patients initially underwent a round of negative intracranial monitoring, but after a second attempt was able to proceed for an at-tempted resection of an epileptogenic focus. Thus, for 10 children (23%), intracranial monitoring did not reveal a resectable seizure focus or a localizable seizure onset, or the family did not want to risk neurological deficit associ-ated with eloquent cortical resection, and these children did not proceed to a therapeutic epilepsy surgery.Preoperative EvaluationWe selected patients for invasive monitoring on the basis of a comprehensive, multidisciplinary evaluation, which included a complete history and physical exami-nation, preoperative MR imaging, and video-monitored scalp EEG. The MR imaging consisted of 1.5-T or 3.0-T studies with a standard high-resolution epilepsy pro-tocol. Other components of the preoperative evaluation included functional MR imaging, interictal PET, ictal SPECT, magnetoencephalography, and Wada testing in some cases. A comprehensive neuropsychological assess-ment established a developmental baseline and assisted with localizing the seizure focus.Surgical Procedure and Postoperative EvaluationThe first procedure involved the implantation of cor-tical electrode grids or strips with or without depth elec-trodes. We typically performed intraoperative ECoG with cortical stimulation motor mapping. The patients then spent one night in the ICU followed by several days in an epilepsy-monitoring unit with continuous video ECoG monitoring.In 10 patients in whom we could not identify an epi-leptogenic focus amenable to further surgery, the second craniotomy involved only the removal of any implanted grids/strips. For the remaining 33 patients in our study group, the second craniotomy involved either a topecto-my of ECoG-localized epileptogenic regions or MSTs (or a combination of the two). All resected specimens were submitted for full histopathological evaluation.Postoperative radiological evaluation included plain films to confirm proper grid/strip placement on the day of initial grid/strip implantation. The 33 study group pa-tients further underwent MR imaging scanning after the second stage of their procedures.Nonlesional epilepsy patients were those in whom no MR imaging evidence of an epileptogenic abnormal-ity could be found. Despite having negative findings on preoperative MR imaging, some patients ultimately were found to have epileptogenic substrates, such as cortical dysplasia or microdysgenesis, on histopathological analy-sis of their resected specimens; we did not exclude these patients from the study, as this histopathologically based diagnosis could not be made preoperatively and would not be useful in the selection of surgical candidates.Data CollectionFinal long-term outcomes were graded utilizing the Engel classification scheme.13 For statistical evaluation, patients were grouped into Engel classes I and II (“good” outcomes) or Engel classes III and IV (unsatisfactory out-comes). Some studies have shown that seizure freedom serves as the most important outcome measure in predict-ing quality of life after epilepsy surgery;18,31 however, re-cent work addressing extratemporal epilepsy surgery has demonstrated that significant psychosocial improvements occur even without a seizure-free result.25,26Positron Emission Tomography and SPECTIn patients for whom PET and SPECT results were available (40/43 and 19/43 patients, respectively), these findings were categorized as being localizing or nonlocal-izing, concordant or discordant with the location of inva-sive grids/strips, and concordant or discordant with the re-gion of resection or MSTs.Magnetoencephalography and Wada TestingBecause magnetoencephalography and Wada testing were employed rarely (1 and 2 cases, respectively), these data were insufficient for analysis.ElectrocorticographyFor patients whose ECoG data were complete and accessible, ictal and interictal activity was categorized as focal, multifocal, or poorly localized. We also noted 1) concordance between ictal and interictal activity and 2) completeness of resection of regions of ictal/interictal activity.

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J Neurosurg: Pediatrics / Volume 7 / February 2011Extratemporal nonlesional epilepsy outcomes181Pathological AnalysisAll resected tissue was submitted for pathological analysis. For statistical evaluation, we grouped these find-ings into normal pathology, focal lesion, or nonspecific inflammation/gliosis.Neuropsychological EvaluationAll patients underwent a preoperative neuropsycho-logical assessment that included standardized measures of intellectual ability, academic achievement, fine mo-tor skills, visual-spatial processing, language processing, memory functioning, and executive functioning. Rating scales completed by parents and teachers (when applica-ble) helped characterize emotional and behavioral func-tioning. A follow-up neuropsychological assessment after surgery quantified changes in functioning and assisted with treatment planning. When possible, measures from the preoperative assessment were repeated at the time of the follow-up assessment. Preoperative data and postop-erative outcome data were compared when possible.Statistical AnalysisPatient data are presented as means with SDs or as a percentage of the number in a given group subset. Probability values for group comparisons were obtained using the chi-square test or Fisher exact test for categorical variables and by unpaired t-test for continuous variables. For analysis of neuropsychological outcomes, 32 neuro-cognitive and neurobehavioral variables were evaluated for pre- and postoperative differences using paired t-tests. Subgroup analyses were also performed to assess for both intragroup differences and pre- versus postoperative dif-ferences for the following subgroups within each of the 32 variables: low and high IQ/performance, Engel class I/II and III/IV, right- and left-sided surgery, frontal and nonfrontal surgery location, and male and female sex.ResultsPatient CharacteristicsOur 33-patient study group was composed of 18 males (54.5%) and 15 females (45.4%). Their mean age was 3.85 years (range 0.17–11 years) at seizure onset and 11.63 years (range 3–19 years) at surgery. The mean dura-tion of epilepsy was 7.64 years (range 0.5–16.25 years). Of note, several of our poor-outcome patients underwent further palliative procedures, including vagal nerve stim-ulator placement (3 patients), corpus callosotomy (1 pa-tient), and reattempted invasive monitoring and topecto-my (1 patient); their outcomes were not affected by these further interventions.Table 1 presents demographic characteristics, preoper-ative seizure characteristics, complications, and procedural data according to Engel class outcome. No significant dif-ferences in demographic variables were noted between the Engel class I/II and III/IV groups.Preoperative EvaluationWhether PET and SPECT findings were localizing, concordant with grid/strip location, or concordant with the ultimate site of resection or MSTs did not show any statistically significant associations with the likelihood of proceeding to therapeutic resection/MSTs or with Engel class outcomes (Tables 2 and 3).Table 4 presents a comparison of ECoG data accord-ing to Engel class outcome. The only significant difference noted between the Engel class I/II and III/IV groups was that the former more frequently experienced a complete re-section of their region of ictal onset. A nonsignificant trend for better outcome was also observed for patients with a complete resection of the zone of interictal epileptiform activity (p = 0.1).Outcomes: Engel ClassFourteen (42.4%) of the 33 patients undergoing ther-apeutic epilepsy surgery with either resection or MSTs achieved an Engel class I outcome, while 18 (54.5%) had either Engel class I or II outcome. Table 5 presents the Engel classification outcomes of all patients and those with more than 2 years’ follow-up.The length of follow-up between groups was also sub-jected to statistical evaluation, and while no significant dif-ference was realized, we did note a nonsignificant trend toward shorter follow-up duration between Engel class I/II patients and Engel class III/IV patients (37.6 ± 23 vs 63.6 ± 46, p = 0.06).Surgery Type and LocationPlease refer to Table 1 for presentation of procedure type and location according to Engel class outcome. Having undergone resection plus MSTs was significantly associated with Engel III/IV outcome (p = 0.004); a significant asso-ciation was also noted (p = 0.05) between having under-gone any MSTs and being in the Engel class III/IV outcome group.Pathologic EvaluationResults of pathological evaluation are also shown in Table 1. The focal lesions that were identified in our patients included cortical dysplasias, microdysgenesis, and subcor-tical white matter heterotopias. No significant differences in Engel class outcome were noted between the normal cortex, focal lesion, and inflammation/gliosis groups.Complications and Postoperative DeficitsThree of the 43 original patients undergoing cranioto-my for invasive monitoring experienced wound infections: one developed a stitch abscess, one suffered a fall that caused acute wound dehiscence and ultimately osteomy-elitis of his bone flap, and another experienced dehiscence of his wound. All of them required simple irrigation and debridement or repeat craniotomy for wound irrigation/de-bridement. Other unexpected returns to the operating room occurred because of symptomatic pneumocephalus in 1 patient, and removal or fracture of electrodes secondary to patient manipulation in 2 others. Other complications in-cluded a case of aseptic meningitis, a frontalis nerve palsy, and a blood transfusion. Overall, complications requiring an unanticipated surgical procedure developed in 6 cases

J Neurosurg: Pediatrics / Volume 7 / February 2011Extratemporal nonlesional epilepsy outcomes183(in 14% of the original 43 patients, or after 7% of the 86 procedures with electrode placement and therapeutic sur-gery and/or removal). In 3 of these cases (7% of patients, 3.5% of procedures) wound infections necessitated a return to the operating room. Some proportion of our patients also experienced ei-ther temporary or permanent neurological deficits after surgery (refer to Table 6 for details of neurological defi-cits), which we consider distinct from surgical complica-tions for reasons to be elaborated in the Discussion. For comparison between Engel classes I and II and classes III and IV with respect to neurological deficits, please refer again to Table 1. No significant differences were noted between groups. Neuropsychological OutcomeTwenty-three patients underwent both pre- and postop-erative comprehensive neuropsychological assessments. The mean interval between the pre- and postoperative assess-ments was 17.65 months (range 8–75 months). Comparison of the performance of the entire sample pre- and postsurgery revealed generally stable intellectual functioning. Overall intelligence remained stable regardless of gender, seizure outcome, or level of preoperative full-scale IQ. Children who had surgery to their left cerebral hemisphere demonstrated significant postsurgical improvements in performance IQ (p = 0.002) that may have been due to primary improvements in their performance on a measure of nonverbal reasoning (p = 0.06). Children who had surgery to their right cerebral hemisphere displayed stable performance IQ scores postsur-gically. For verbal IQ, no significant changes were observed following either left-sided or right-sided surgery, and no changes in intellectual performance were noted based upon TABLE 1: Demographic and characteristics by Engel class (I/II vs III/IV)* (continued)VariablePostop Engel Classp Value I & II (18 patients)III & IV (15 patients)procedure (continued) resection & MSTs no yes frontal resection no yes parietal resection no yes occipital resection no yes0.004†¶18 (100)09 (60)6 (40)0.747 (39)11 (61)5 (33)10 (67)1.0†16 (89)2 (11)13 (87)2 (13)1.0†15 (83)3 (17)13 (87)2 (13)* Data are numbers of patients (% of group) unless otherwise indicated. Means are given with SDs. Probability values are for comparison of groups by chi-square test (for categorical variables) or unpaired t-test (for continuous variables), unless otherwise indicated. Patients with both permanent and temporary complications are classified in the permanent category. Abbreviation: FU = follow-up.† By Fisher exact test or Wilcoxon test (for yearly seizure burden).‡ Percentages based on the 33 patients undergoing resection/MSTs, not the total of 43 who underwent invasive monitoring.§ By Cochran-Armitage trend test.¶ Statistically significant.TABLE 2: Association of PET and SPECT variables with having undergone a therapeutic procedure*VariableTherapeutic ProcedureNop Value†YesPET localizing no yesPET concordant w/ grid/strip location no yesSPECT localizing no yesSPECT concordant w/ grid/strip location no yes 0.276/10 (60)4/10 (40)11/30 (37)19/30 (63) 0.157/10 (70)3/10 (30)

I. G. Dorward et al.184 J Neurosurg: Pediatrics / Volume 7 / February 2011the location of the surgery (that is, frontal or nonfrontal). Nevertheless, there was a trend toward improved perfor-mance on an intellectual measure of verbal abstract reason-ing among all children who achieved better seizure control (p = 0.07).Further analyses of neuropsychological outcomes revealed unchanged performance in most domains. On a measure of verbal learning using the California Verbal Learning Test, learning efficiency and long-term recall remained unchanged, regardless of sex, surgery location, prior level of functioning, or seizure outcome. The same was true on measures of visual memory. However, children with poorer seizure outcome after surgery (Engel Class III or IV) displayed a significant decline in their abilities to recall structured verbal information (stories) (p = 0.04). In terms of executive functioning, significant improvements in immediate auditory attention were observed for the en-tire sample (p = 0.05), and further analyses suggested a trend toward improved attention among children who had surgery to their right cerebral hemisphere (p = 0.08).DiscussionMultiple studies have documented the efficacy of re-sective epilepsy surgery, with 2 principal determinants of success: whether a discrete resectable lesion exists, and whether the targeted epileptogenic region is in a temporal or extratemporal location. Evidence has begun to accumu-late regarding the treatment of patients with extratemporal, nonlesional epilepsy. Surgery for these patients has gen-erally yielded Engel class I or II outcomes in 33%–61% of patients. However, one study—similar in design to our study, but in patients aged 8–28 years—showed excellent outcomes, with 81% of patients rendered seizure-free and all patients having a > 90% reduction in seizures;10 their sample size was relatively small (16 patients), and this de-gree of success has not been duplicated in other studies. Aside from this study, our 54.5% rate of Engel class I and II outcomes compares favorably with other findings in the literature, including a recent meta-analysis of extratempo-ral, nonlesional epilepsy surgery in which an overall 48.4% rate of Engel I or II outcomes was obtained for 95 patients in 17 retrospective studies.1 Of course the surgeon’s selec-tion of operative candidates may substantially impact out-come in these cases, and as such has the potential to intro-duce selection bias in this and any related study. Unlike these previous studies, however, we have included only pediatric patients, thereby improving the generalizability of our results for the pediatric population.The principal utility of this study is to support further the idea that good or excellent outcomes can be obtained in extratemporal, nonlesional epilepsy cases despite what is often thought to be a poor surgical prognosis. Our findings may also prove useful to epilepsy surgeons in counseling families regarding the likelihood of seizure freedom or amelioration following surgery. An impor-tant point of emphasis is the potential for subjecting the patient to invasive monitoring with subdural grids and strips, yet finding no region of epileptogenic cortex ame-nable to topectomy or MSTs. In our study, 43 patients un-derwent invasive monitoring, with only 33 proceeding to therapeutic epilepsy surgery; thus our patients had a 23% risk of undergoing an invasive study with negative results. This compares with our earlier series of 112 consecutive patients undergoing invasive monitoring in the study by Johnston et al.16 in which 17 (15.2%) of 112 patients did not proceed to a therapeutic procedure. If we include the next 29 consecutive invasively monitored patients since the cut-off date of the aforementioned study, this rate drops to 17 of 141, or 12.1%. This risk of negative results from invasive monitoring is consistent with the challeng-ing surgical management of extratemporal, nonlesional epilepsy, and must be emphasized to patients and families to create realistic expectations.We did not identify any preoperative prognostic fac-tors to identify patients who would most likely benefit from invasive monitoring or from a therapeutic resec-tion or MST. The results of PET and SPECT, though not available in all cases, showed no association with either the likelihood of proceeding to a therapeutic surgery following invasive monitoring or with Engel Class out-come. This negative finding suggests that in the subset of patients with extratemporal, nonlesional epilepsy, these preoperative diagnostic adjuncts may not contribute sub-stantially to surgical decision making. However, such a TABLE 3: Association of PET and SPECT variables with Engel Class in patients who have undergone a therapeutic procedureVariableEngel ClassI or II (18 patients)p Value*III or IV (15 patients)PET localizing no yesPET concordant w/ resection/ MSTs no yesPET concordant w/ grid/strip location no yesSPECT localizing no yesSPECT concordant w/ resection/ MSTs no yesSPECT concordant w/ grid/strip location no yes 0.76/15 (40)9/15 (60)

J Neurosurg: Pediatrics / Volume 7 / February 2011Extratemporal nonlesional epilepsy outcomes185conclusion would need to be validated in a larger series of patients. Further, regarding invasive ECoG data, we noted that only the completeness of resection of a region of ictal onset correlated with improved outcome; this re-sult corroborates earlier findings.7 A nonsignificant trend was also noted between completeness of resection of the interictal zone of activity and improved Engel class out-come, and we might anticipate a more robust result with a larger sample size. We did not find any particular electri-cal characteristics on preoperative EEG or intraoperative ECoG that correlated with outcomes. In contrast, a re-cent study showed that focal high-frequency oscillations at seizure onset correlated with increased likelihood of Engel class I outcomes.29An important design element in this study is that we selected “nonlesional” patients on the basis of preop-erative MR imaging alone. This approach contrasts with some other studies in which the determination of lesional versus nonlesional status was made on the basis of patho-logical findings. We consider the former approach more clinically useful, as MR imaging is readily available in the period of preoperative assessment and is vital in de-termining optimal candidates for epilepsy surgery and in counseling patients and families. Of course, utilizing imaging rather than pathology to make the determination of “lesional” versus “nonlesional” might lead to the inclu-sion in our study of some patients who would have been excluded from previous studies.7 On the other hand, com-pleteness of resection is an important determinant of out-come with epileptogenic lesions; the fact that we lacked imaging to guide the completeness of resection could be seen as a cause of worse outcomes. In sum, our method of defining “nonlesional” cases might introduce bias, but the direction of this bias remains unclear.One important limitation of our study relates to the duration of follow-up, which varied somewhat (though nonsignificantly, p = 0.06) between our outcome groups, with Engel class I and II patients having shorter duration of postoperative follow-up. This factor could bias our re-sults, as some of these seizure-free or “good outcome” pa-tients might have manifested worse clinical outcomes had our follow-up duration been longer. On the other hand, if a patient’s epilepsy has been “cured” or significantly ame-liorated, the patient’s parents might be less likely to make the effort to maintain contact with the epilepsy manage-ment team. Thus, while this shorter follow-up duration in patients with good or excellent outcome represents a source of possible bias, it may be the direct result of those better outcomes.A certain number of our findings were notable in that TABLE 5: Outcomes of surgery (Engel classification)Engel ClassAll Patients (33 patients)Patients w/ >2 yrs FU (22 patients)IIIIIIIV14 (42)4 (12)10 (30)5 (15)8 (36)3 (14)7 (32)4 (18)TABLE 4: Comparison of ECOG data by Engel class in 26 patients*VariableEngel Classp ValueI or II (14 patients) III or IV (12 patients)ictal onset focal, multifocal, or poorly localized focal multifocal poorly localizedinterictal onset focal, multifocal, or poorly localized focal multifocal poorly localizedictal activity matches interictal activity no yesictal onset completely resected no yesinterictal activity region completely resected no yes 1.0†9 (64)2 (14)2 (21)

5 (36)7 (50)2 (14)

7 (50)7 (50)

2 (14)12 (86)

6 (43)8 (57)7 (58)2 (17)3 (25)

4 (33)5 (42)3 (25)

7 (58)5 (42)

6 (50)6 (50)

9 (75)3 (25)

0.88†

0.67

0.05‡

0.1

* Data are the number of patients (percentage of group). Unless otherwise indicated, p values are for comparison of groups by chi-square test.† Due to sparse data in the cross-tabulations, p values by Fisher exact test.‡ Significant at the p = 0.05 level.

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I. G. Dorward et al.186 J Neurosurg: Pediatrics / Volume 7 / February 2011they did not show significant association with seizure out-come. For instance, we did not note that outcomes cor-related with preoperative seizure frequency or duration, though these relationships have been established in ex-tratemporal epilepsy surgery;8,9 this finding likely stems from the relatively small sample of patients meeting in-clusion criteria for our study (compared with 81 and 399 patients, respectively, in the referenced studies), as well as the heterogeneity of our study population. Further, the presence of a pathological abnormality in the resected specimen—such as focal cortical dysplasia, microdysgen-esis, or heterotopia—did not correlate with seizure out-come. While our study may have been underpowered to detect a difference between groups, these results suggest that from the standpoint of “lesional” epilepsy, the fact of a lesion being radiographically evident on MR imag-ing may be more clinically significant than its presence upon pathological study. Pertinent to this issue, it must be noted that none of our patients’ pathological samples showed neoplasia, the presence of which has been shown to be useful in predicting outcomes for extratemporal epi-lepsy surgery.8 A recent study33 found a significant cor-relation between nonneoplastic focal lesions and surgical outcome, but 94% of these lesions were apparent on pre-operative MR images.Multiple Subpial TransectionsOne of the other significant findings in this study was that patients who underwent MSTs were more likely to have a poor seizure outcome. These data should not necessarily impugn the efficacy of MSTs—which has been addressed elsewhere4,6,11,19–22,24,32—as the study was neither designed nor adequately powered to address that issue. However, the fact of MSTs having been performed may be a negative predictor of outcome because their use indicates that a region of ictal onset or early spread remains in situ. At our institution, previous work2 has demonstrated that in patients with rolandic epilepsy, to-pectomy is superior to MST for seizure outcome, but that MSTs can be performed safely in eloquent cortex, without resultant deficits. Thus, at our institution MSTs are performed in patients with ictal onset or early spread involving eloquent cortex, the resection of which would likely result in a neurological deficit. If, after extensive family discussion, the preference is to err on the side of avoiding neurological deficit even if it means leaving potentially epileptogenic tissue in place, then we tend to offer MSTs as a safer alternative, albeit one that is in-ferior from the standpoint of seizure control. Our find-ings in this study do not generally add to the knowledge regarding MSTs, except to say that in this group of pa-tients with extratemporal, nonlesional epilepsy they were largely ineffective—hence the association with Grade III/IV outcomes—except for one successful case (one patient with a Grade I outcome had exclusively MSTs). Further, as in our institution’s previous study of rolandic epilepsy,2 MSTs were generally safe, with no neurological deficits directly attributable to their use.Neuropsychological OutcomesOur results suggest generally favorable neurocogni-tive outcomes in children who undergo nonlesional, ex-tratemporal lobe epilepsy surgery, with stable intellectual functioning in the sample as a whole and evidence of improvements in specific aspects of intelligence (that is, performance IQ) among children who undergo surgery to TABLE 6: Neurological deficits associated with topectomy*Case No.Age (yrs) Op Neurological DeficitFU (mos)Status at Final FUEngel Class12345678914511716121817168317occipital cortex resectionfrontal cortex resectionfrontal cortex resectionoccipital cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal cortex resectionoccipital cortex resectionfrontal/parietal cortex resection expressive aphasialt homonymous hemianopsiasupplementary motor area syndromelt hemiparesislt lat visual field deficitBroca aphasiasupplementary motor area syndromesupplementary motor area syndromelt hemiparesislt hemiparesissupplementary motor area syndromevisual field deficit2725741479372037671202539subtle persistent visual field defect no residual deficitleft spastic hemiparesis, 3–4/5 strengthpersistent deficitno residual deficitno residual deficitno residual deficit4+/5 lt UE paresisno residual deficitno residual deficitno residual deficitpersistent but improved speech fluency deficitpersistent but improved right hemiparesisimproved but persistent rt UE paresispersistent but improved left hemiparesisslight hyperreflexivity but no motor deficitmild persistent facial paresisIIIIIIIIIIIIIIIIIIII1011121314151617191071712frontal cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal cortex resectionfrontal/parietal cortex resection lt facial paresisrt hemiparesisexacerbation of preexisting rt UE paresislt hemiparesissupplementary motor area syndrome42201644217IIIIIVIIV* UE = upper extremity.

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J Neurosurg: Pediatrics / Volume 7 / February 2011Extratemporal nonlesional epilepsy outcomes187their left cerebral hemisphere. It is possible that children who underwent left-sided surgery may have experienced significant improvements in nonverbal reasoning (that is, matrix reasoning) secondary to reduced seizure activ-ity in their right cerebral hemisphere; improved seizure control may have allowed their unaffected cerebral hemi-sphere to function more efficiently. Unfortunately, the va-lidity of this conclusion cannot be definitively evaluated due to limited information about functional organization in the present sample (that is, hemispheric dominance).Patients displayed generally stable neurocognitive performance in other areas as well. No significant chang-es were observed in visual-spatial processing or language processing, and most aspects of memory functioning re-mained well-preserved following surgery. Children with Engel Class III or IV outcomes did demonstrate a sig-nificant decline in their ability to recall meaningful ver-bal information (stories), though this decline was not ob-served in other subsamples in the current study. It is pos-sible that children with poor seizure outcome, left-sided surgery, and/or low presurgical intelligence may be at risk for poorer verbal memory outcomes, though further in-vestigation would be necessary to explore this conclusion. It should also be noted that this decline in verbal memory may reflect cognitive side effects from the AED regimen of children with poor seizure outcomes, as AEDs are known to impact memory and executive function.28Declines in executive functioning are one of the most prominent concerns when considering extratemporal sur-gery, particularly when the frontal lobes are involved. Our results do not show declines in executive functioning, but instead highlight improvements in selected aspects there-of. For example, the previously discussed improvement in nonverbal reasoning among children who underwent left-sided surgery may suggest benefits in aspects of executive functioning that are not anatomically associated with the location of the surgery. Moreover, our results reveal signifi-cant improvements in immediate auditory attention (digit span) for the entire sample, with a trend toward specific improvements among children who underwent surgery to their right cerebral hemisphere. While this finding is encouraging, we should emphasize that the impact of re-ductions in AEDs among children who experienced bet-ter seizure outcomes cannot be ruled out as a contributing factor. Importantly, the current study also does not provide information about emotional and/or behavioral outcomes among children who undergo surgery. Children with epi-lepsy, especially intractable epilepsy,27 are at increased risk for internalizing psychopathology (such as depression and anxiety). Therefore, improvements in attention may occur in accordance with the improvements in emotional func-tioning associated with better seizure control.In evaluating our neuropsychological results, it should be noted that we performed a large number of statistical tests in exploring the interactions between patient subsam-ples and various neurocognitive evaluations; as such, the likelihood of obtaining falsely positive statistical correla-tions is increased.Complications and Postoperative DeficitsA salient feature of our results is the seemingly large proportion of patients sustaining either a temporary (28%) or permanent (32%) neurological deficit. It is essen-tial to understand that, in this series, all but one (a tran-sient frontalis palsy) of these outcomes were predictable on the basis of the procedure performed, and were fully discussed with the patient and family prior to proceeding. The nature of surgery in this group of epilepsy patients is that resection of epileptogenic cortex necessarily im-plies some loss of function; in ideal circumstances this loss of function is clinically silent, but in some cases it involves an expected postoperative deficit. This inherent trade-off of function for possible seizure amelioration is something that must be discussed at length with patients and families in the course of preoperative counseling and decision making. In any event, in those cases in which deficits were expected, we did not look upon temporary or permanent deficits as complications per se, because of their inherent predictability. On the other hand, our pa-tients suffered 3 wound infections and 3 additional com-plications, leading to a 14% risk per patient, or a 7% risk per procedure, of unpredicted complications; when the need for electrode repositioning is excluded, our rate falls to 9.3% of patients or 4.7% of procedures. Overall, our complication rate is somewhat higher than the 4%–5.4% rate reported in some larger studies of epilepsy surgery,3,9 but it remains relatively close to the 7.4% rate of compli-cations requiring reoperation (not including reoperation for grid/strip adjustment) in our recently published expe-rience with invasive monitoring in 112 procedures.16ConclusionsSurgery for seizures of extratemporal, nonlesional origin remains challenging. In this pediatric-only study, we have demonstrated that these patients are viable can-didates for invasive monitoring with grid/strip electrodes, and good outcomes can be obtained with resective sur-gery. Important points to highlight in preoperative dis-cussions with patients and families include the risk of invasive monitoring without a subsequent therapeutic procedure and the possibility of incurring a minor neuro-logical deficit as a trade-off for a chance at seizure ame-lioration. DisclosureThe authors report no conflict of interest concerning the mate-rials or methods used in this study or the findings specified in this paper.Author contributions to the study and manuscript preparation include the following. Conception and design: Smyth, Dorward, Titus. Acquisition of data: Dorward, Johnston, Titus. Analysis and interpretation of data: Smyth, Dorward, Titus, Johnston, Bertrand. Drafting the article: Dorward. Critically revising the article: Smyth, Dorward. Reviewed final version of the manuscript and approved it for submission: all authors. Administrative/technical/material sup-port: Dorward. Study supervision: Smyth.AcknowledgmentsThe authors acknowledge Karen Steger-May for assistance with statistical evaluations and Karen Dodson for assistance with manuscript preparation.